small renal masses: incidental diagnosis, clinical...

Hindawi Publishing CorporationAdvances in UrologyVolume 2008, Article ID 310694, 6 pagesdoi:10.1155/2008/310694

Review ArticleSmall Renal Masses: Incidental Diagnosis, Clinical Symptoms,and Prognostic Factors

F. M. Sanchez-Martın,1 F. Millan-Rodrıguez,1 G. Urdaneta-Pignalosa,1 J. Rubio-Briones,2

and H. Villavicencio-Mavrich1

1 Servicio de Urologıa, Fundacio Puigvert, C/Cartagena 340, 08025 Barcelona, Spain2 Servicio de Urologıa, Instituto Valenciano de Oncologıa, C/Beltran Baguena 8, 46009 Valencia, Spain

Correspondence should be addressed to F. M. Sanchez-Martın, [email protected]

Received 13 May 2008; Revised 26 September 2008; Accepted 18 November 2008

Recommended by Maxwell V. Meng

Introduction. The small renal masses (SRMs) have increased over the past two decades due to more liberal use of imagingtechniques. SRMs have allowed discussions regarding their prognostic, diagnosis, and therapeutic approach. Materials andmethods. Clinical presentation, incidental diagnosis, and prognosis factors of SRMs are discussed in this review. Results. SRMsare defined as lesions less than 4 cm in diameter. SRM could be benign, and most malignant SMRs are low stage and low grade.Clinical symptoms like hematuria are very rare, being diagnosed by chance (incidental) in most cases. Size, stage, and grade arestill the most consistent prognosis factors in (RCC). An enhanced contrast SRM that grows during active surveillance is clearlymalignant, and its aggressive potential increases in those greater than 3 cm. Clear cell carcinoma is the most frequent cellular typeof malign SRM. Conclusions. Only some SRMs are benign. The great majority of malign SRMs have good prognosis (low stageand grade, no metastasis) with open or laparoscopic surgical treatment (nephron sparing techniques). Active surveillance is anaccepted attitude in selected cases.

Copyright © 2008 F. M. Sanchez-Martın et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

1. INTRODUCTION

The incidence of renal cell carcinoma (RCC) has increasedover the past two decades reflecting earlier diagnosis at anearlier stage, largely due to more liberal use of radiologicalimaging techniques [1], introducing concepts as “incidental”or “small renal masses” (SRMs). SRM could be definedas those renal masses lower than 4 cm in diameter [2–4],accounting for 48–66% of RCC diagnosis [5]. Actually, 79–84% of SRM are detected before genitourinary symptomsare present [6–8] (size is smaller than symptomatic cancerclassifying it as local stage with a better prognosis) [9].Although mean tumor size has decreased in the last years,several studies indicate that this variable is one of themost important prognosis factors for RCC, and it has alsocontributed to the last modifications of RCC staging andtreatment [10, 11].

Years ago, when most RCC were symptomatic, hematuriawas the main symptom, so asymptomatic tumors werediagnosed later or not diagnosed. Before widespread use

of imaging techniques, 67–74% of RCC remained unde-tected until death (autopsies), and only 8.9–20.0% of theseundiagnosed RCC were responsible for the patient’s death[5]. These data support the fact that some RCC have afavorable evolution and support active surveillance in selectcases. Natural history of SRM has not been historically wellestablished because most masses were surgically removedsoon after diagnosis.

2. DEFINITIONS AND GENERAL CONCEPTS

A renal mass discovered by routine ultrasound, CT or MRindicated for other pathology, could be named incidental.A significant number of SRMs are incidentally diagnosed[2, 12]. Renal masses (benign and malign) can be consideredincidental if they are diagnosed in the absence of symptomsor signs. “Incidentaloma” or “incidental” masses relatedto other organs such as adrenal, pituitary, thyroid andparathyroid, as well as the liver are published. Mirilasand Skandalakis questioned the scientific justification for

2 Advances in Urology

this neologism and suggested that should be replaced by“incidentally found” [13]. Narrow relation of “incidental”and “small masses” are considered in some papers [2, 14–16].A possible confusion factor may be that tumors classified as“incidental” show symptoms not directly attributable to therenal mass, thus not detected by the urologist [5].

Small renal masses include all solid or complex cysticlesions lower than 4 cm. Among them, different benigntumors are found in a 12.8 to 17.3% of cases [17–19] includ-ing oncocytoma in 53%, angiomyolipoma in 22%, atypicalcyst in 10%, and different benign lesions as leiomyoma,xanthogranulomatous pyelonephritis, and focal infarction in13% [17].

Incidental renal tumors have a mean size of 3.7 cm(median 3, range 0.8 to 12) [7]. Nevertheless, tumorsgreater than 4 cm could be incidental. Incidental diagnosisis performed in the 82.4%, 78.9%, and 56.7% of the 1–4 cm,4–6 cm and greater than 6 cm renal masses, respectively [5].If a cut-off should be made, most cases of RCC lower than7 cm are incidentally discovered, while tumors greater than7 cm are mainly symptomatic but, as mentioned previously,this cannot be taken as a rule [7].

3. SYMPTOMS

The main symptom of RCC is hematuria (35%–60%)[20–22] but SRMs are often asymptomatic (incidental).Classical manifestations of RCC such as fever or jaundice areextremely rare in front of an SRM. In a study of 349 SRM’s,microhematuria was reported in only 8 cases. Prognosticof those RCC diagnosed by hematuria is worse than thoseincidentally diagnosed [23]. Stage I lesions were observed in62.1% of patients with incidental RCC renal cell carcinomaand just in 23% with symptomatic RCC [6]. Among thedifferent entities causing the incidental diagnosis of an SRM,many have been considered; evaluation for other malignancy(17.7%), gastrointestinal symptoms including nonspecificabdominal pain (16%), evaluation of medical renal disease(6.6%), hypertension (4%), back pain (5.1%), cirrhosis(1.4%), nephrolithiasis (1.4%), diverticulitis (1.4%), lunglesion (1.1%), increased liver enzymes (1.1%), trauma(0.8%), screening CT (0.8%), urinary tract infection (0.8%),chest pain (0.8%), aortic aneurysm evaluation (0.8%), cough(0.5%), shortness of breath (0.5%), Crohn’s disease (0.5%),bronchocele (0.5%), and anemia (0.5%). No differences werefound among incidental or symptomatic RCC according toage, sex, and laterality [15].

Laboratory findings have a significant impact on thepatients with organ-confined RCC prognosis. Although,neoplasic condition reflects an increased invasive potential,characterized by overexpression of substances involved incell proliferation as matrix metalloproteinases [24]; how-ever, inflammatory markers like erythrocyte sedimentationrate greater than 30 mm/hour, hemoglobin levels less than10 gm/dL (female) or 12 gm/dL (male), and increased alka-line phosphatase are negative prognosis elements [22].

Some demographic data may help to presume the matterof SRM: RCC is unusual in young patients; angiomyolipomas

and multilocular cystic nephromas are more common inwomen [25].

4. PROGNOSIS FACTORS

Age is not a significant factor on survival in patients withincidental RCC [26], so it is probably not a prognosis factorfor SRM [5]. However, as the patient ages, the SMR stage ishigher; so the incidence of SRM finally staged as pT3 tumorsin younger than 45 years, 45–75 years, and older than 75 yearsis 2.3%, 6.9%, and 14.3%, respectively [17]. The probabilityof developing metastases, with 12 years follow-up, is greaterin men [27].

5. BENIGN TUMOR FREQUENCY

Lee et al. published 230 cases of SRM (lower than 4 cm),88% malignant and 12% benign (oncocytoma) [6]. DeRocheet al. described that SRMs are nonneoplasic entities. Benignneoplasms and low-and high-grade carcinoma accountedfor 1.6%, 18.0%, 49.0%, and 31.4%, respectively [8]. Thepercentage of malignancies increases from 72.1% in masseslower than 2 cm to 93.7% in tumors greater than 7 cm [7].

In conclusion, if the tumor is greater in dimensions, thepossibility of being benign is lower; so tumors lower than1, 2, 3, and 4 cm were benign in 46.3, 22.4, 22, and 19.9%,respectively [18].

6. SIZE AND STAGE

In a study from Schlomer et al., global mean renal tumorsize decreased by 32% and pT1 tumors increased from 4%to 22% (1989–1998). For every cm increase in size, theodds ratio of malignancy increased 17–39% [7, 18]. Meantumor size for benign tumors was 4.2 cm (median 3.3, range0.2–25) compared to 6.3 cm (median 5.5, range 0.1–24) formalignant tumors. Median clinical diameter was 2.93 cm(range 0.8 to 4.0) in RCC lower than 4 cm. RCC meansize was 4.6 cm (range 0.8–21) and benign masses meansize 2.8 cm (range 0.8–9.5) [5]. Incidental RCC mean sizewas 3.7 cm (median 3, range 0.8–12) and symptomatic RCCmean size was 6.2 cm [7]. In pathological stage, 51.33% and27.3% were pT1, 25.6% and 27.3% pT2, 10.9% and 23.8%pT3a, 10.9% and 16.6% pT3b, 1.2% and 2.3% pT3c, and0% and 2.3% pT4 in incidental and symptomatic RCC,respectively.

Puppo et al. reported 94 patients with resected RCC (size:1.1–4.5 cm), describing that pathological stage was pT1a in92.5%, pT1b in 4.2%, and pT3a in 3.1% [28], similar toPahernik et al. that reports pT1a in 84.5%, pT1b in 8%, andpT3 in 7.5% (organ confined in 92.5%) and≥pT3 was foundin 3.0%, 5.1%, and 12.1% of the patients when analyzed bytumor size 2, 3, and 4 cm, respectively [17]. A total of 25%of SRM doubled in volume within 12 months, 34% reached4 cm and experienced rapid doubling time [5].

Kunkle et al. found synchronous metastatic diseaseincreased by 22% with each cm increase in tumor size, by50% for each increase of 2 cm, and doubled for each 3.5 cmincrease in primary tumor size [11].

F. M. Sanchez-Martın et al. 3

In other manuscript, incidental RCC had lower stagescompared to symptomatic RCC [15]. Between T1a and T1blesions, there was no significant difference in the rate ofmalignancy and high-grade malignancy regarding incidentalor symptomatic presentation. The different percentage of T2malignant tumors between incidental (90.9%) and symp-tomatic tumors was neither significant [5]. Understagingfor pT3 tumors lower than 3 cm was 7.5% [17]. Cysticcomponent appears in 24.1% of renal masses lower than4 cm, being 57.1% in Bosniak type III and the rest in Bosniaktype IV [5].

Volpe et al. showed no differences between the averagegrowth rate for solid SRM (0.11 cm per year) and cysticmasses (0.09 cm per year) [5]. Multifocality was present in5.3–12% in small RCC [7, 8]. The rate of multifocalitywas 2.0%, 5.1%, and 7.05% in tumors of 2, 3, and 4 cm,respectively [17].

7. GRADE

Ninety percent of tumors lower than 1 cm were low-gradecompared to only 37.9% of tumors ≥7 cm [18]. Grade 3was found in 7.1%, 9.0%, and 14.0% of the patients in the2, 3, and 4 cm groups, respectively and just 10.6% of smallRCC were grade 3 [17]. Tumor grade increase as tumorsize increase from 2 to 4 cm. Grade 1 was 31.3% for 2 cm,27.4% for 3 cm, and 18.1% for 4 cm tumors; and grade 3 was7.1% for 2 cm, 9% for 3 cm, and 14% for 4 cm tumors [17].Urinary tract invasion, reported in some low-grade tumors,is a negative prognostic factor [29]. However, 45% of T2incidental malignancies were high grade compared to 78.8%of T2 symptomatic malignancies [5]. Tumor grade increasedaccording to size in clear cell, papillary, and chromophobetumors. In high-grade carcinomas, 65% of the tumors had a1-year volume doubling time.

8. CELLULAR TYPE

Clear cell is the most frequent cellular type regardless oftumor size [7]. Among SRM, Frank et al. showed thatpercentage of clear cell cellular type increased according tosize: 59.9, 70.2, and 72% in lower than 2, 3, and 4 cm,respectively [18]. Cellular type for small RCC was 78%clear cell carcinoma, 15.3% papillary carcinoma, and 7%chromophobe carcinoma [17].

Volpe et al. showed that papillary RCC incidence is morefrequent in 2 cm tumors than in 3 and 4 cm tumors (24%,13.2%, and 13.5%, resp.) [17]; data not refuted by otherauthors [5]. Papillary cell type is more frequent than clearcell in tumors lower than 1 cm [18].

9. METASTASES

Metastases at diagnosis were found in 3.0%, 2.6%, and6.0% of the patients with 2, 3, and 4 cm renal tumors,respectively [17]. Furthermore, lymph node spread was 4.8%and 15%, metastasis was 9.2% and 26%, and local recurrencewas 1.2% and 8.3%, among incidental and symptomaticRCC, respectively [15]. With active surveillance, enhancing

lesions with zero median growth rates did not progress tometastatic disease, and only 1.4% of patients with 0.31 cmyearly median growth rate progressed to metastatic disease[7]. Chawla et al. showed RCC mean growth rate of 0.40 cmyearly (median 0.35, range 0.42 to 1.6) [30].

Median tumor size for patients presented with patho-logically confirmed synchronous metastatic disease wassignificantly greater than for those presenting with localizeddisease, 8.0 cm (range 2.2 to 20.0) and 4.5 cm (range 0.3to 17.5), respectively. Tumors of 3.0 cm or smaller hadsynchronous metastasis in just 4.5% of the cases [31].

10. SURVIVAL

A total of 548 patients with small RCC were analyzed byPahernik et al.: 22 (4%) had metastasis, 9 died by cancer in amean time of 1.9 years (range 0.7 to 3.4) after diagnosis [17].D’allOglio et al. observed a mean overall survival of 91% inpatients with T1a tumors and up to 78.7% survival after 10years of local treatment [15].

Several groups have developed predictive models toconstruct prognosis algorithms in order to facilitate follow-up and to indentify progression risk. Raj et al. present apredictive model that includes gender, symptoms, radiolog-ical findings, and size as preoperative prognostic factors; inorder to establish a chance of being cancer-free 12 years aftersurgery (Figure 1). In case of SRM, it could not be usefulto decide surveillance or active treatment. For example, awoman with a 3 cm incidental malign SRM has a 96% chanceof being cancer-free 12 years after surgery. In contrast, aman with a 4 cm symptomatic (local signs) malign SRM andpositive TC showing enlarged lymph nodes has 60% chanceof being cancer-free 12 years after surgery [27].

Classically, better prognosis has been assigned to inci-dental diagnosis, papillary or chromophobe pathology, smallsize, and early stage [32]. Presence of necrosis and vascularinvasion is useful in a specific algorithm looked toward clearcell renal tumor [33].

Table 1 resumes the main prognosis factors useful onSRM.

11. TREATMENT AS PROGNOSIS FACTOR

Size is a significant factor in the decision to perform NSS:tumors sized 2 cm (81%), 3 cm (73%), and 4 cm (44%)cm could be treated by means of NSS. This treatment istechnically easier in incidental than not incidental RCC (76%versus 24%) [15]. Local excision is a safe treatment for smallRCC, even in extreme cases such as living donor kidneywith a 5 × 5 mm RCC found on its surface [34]. In patientswith RCC lower 4 cm, who underwent partial or radicalnephrectomy 14% and 10% died during follow-up (cancer-specific death occurred in 3% in both approaches). Diseasespecific survival rate at 3 and 5 years is 95 and 97% in partialand radical nephrectomy, respectively [6].

When active surveillance is applied to 2 cm meansize contrast-enhancing renal masses, no differences werereported about age, sex, initial size, and solid versus cysticradiologic appearance. A significant different frequency


0 10 20 30 40 50 60 70 80 90 100

M

F

Located

SystemicIncidental

Points

Gender

Mode ofpresentation

Y

N

Lymph nodeby imaging

Necrosisby imaging

Y

N

Size byimaging (cm)

0 1 2 3 4 5 6 7 9 13

Total points 0 20 40 60 80 100 120 140 160 180

12-yearmetastasis free

probability0.99 0.98 0.95 0.9 0.7 0.5 0.3 0.1 0.01

Figure 1: Preoperatory prognosis RCC nomogram [27].

Table 1: Small RCC prognosis factors.

Better prognosis Worse prognostic

Incidental Symptoms

Small size <3 cm Size > 3 cm

T1 T2 and >

Low grade High grade

No upper tract invasion Upper tract invasion

No lymph nodes Necrosis

No necrosis Lymph nodes

No vascular invasion Vascular invasion

Negative biological markers Positive biological markers

Papillary or chromophobepathology (¿)

Sarcomatoid component

Zero median grown rate Grown rate > 0.31 cm yearly

Option to NSS No option to NSS

of surgery was found among tumors with 0 or 0.31 cmmean yearly growth rate of 17% and 51%, respectively [7].However, 33% of SRM under active surveillance showedzero or negative radiologic growth [7]. The probability todevelop metastasis in masses lower than 3 cm managed byactive surveillance was only 2% [14]. Prior and duringfollow-up, renal tumor biopsies are recommended. As ageneral rule, biopsy may be indicated in masses that havefeatures of oncocytoma in poor surgical candidates. Forpatients who have a surgical contraindication or rejectsurgery, alternative ablation techniques can be proposed(cryoablation, radiofrequency) [35].

For Kassouf et al., 20.8% of renal masses showed tumorgrowth during the surveillance period (mean 31.6 months),but neither of them developed metastasis. Patients receiving

surgical treatment after surveillance did not modify theirprognostic [16]. Hereditary renal tumors may have a moreaggressive natural history, and thus surveillance should bemade with caution. Meta-analysis of Kunkle et al. observedno statistical differences in the incidence of SRM progressionregardless excision, ablation, or active surveillance [2].

12. CONCLUSIONS

SRMs are those smaller than 4 cm, often incidentally diag-nosed. Clinical symptoms, like hematuria, are rare, butconfer worse prognosis. Size, stage, and grade are still themost consistent prognostic factors in RCC. It is importantto keep in mind that SRM could be benign tumors, mainlyoncocytoma. Most malign SMRs are low stage and low grade,without metastatic spread if diameter is below 2-3 cm. Clearcell carcinoma is the most frequent cellular type of malignSRM. Papillary tumors are more frequent when SRM size isless than 1 cm, having a better prognosis. Aggressive potentialof small RCC could increase in tumors greater than 3 cm,so it is suggested that the threshold for selecting patients(old age, high-risk, solitary kidney, reject surgery) for asurveillance strategy should be set well below a tumor sizeof 3 cm. In active surveillance, the size increase of an SRM isa strong indicator of malignancy; helping to decide a surgicaltreatment.

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